Background: Insulin resistance is associated with cardiovascular morbidity and mortality in the general population. However, the relationship between insulin resistance and health outcomes is controversial in patients with impaired renal function. Our study aimed to investigate the association between insulin resistance and prognosis in a cohort of non-diabetic stroke patients with different estimated glomerular filtration rate (eGFR) strata. Methods: Data were derived from Abnormal Glucose Regulation in Patients with Acute Stroke across China (ACROSS-China) registry. Ischemic stroke patients without history of diabetes were included. Fasting and oral glucose tolerance test (OGTT)-derived measures of insulin resistance were calculated along with homeostasis model assessment of insulin resistance (HOMA-IR) and composite insulin sensitivity index (ISI). Insulin resistance was defined by the highest HOMA-IR quartile (Q4) and the lowest composite ISI quartile (Q1). Results: Among 1,196 patients, HOMA-IR Q4 (insulin resistance) vs. Q1-3 was associated with increased 1-year mortality (adjusted hazards ratio [HR] 1.83, 95% CI 1.07-3.13) and poor functional outcome (adjusted OR 1.97, 95% CI 1.32-2.95) only in participants with an eGFR 90 mL/min/1.73 m(2). By comparison, composite ISI Q1 (insulin resistance) vs. Q2-4 was associated with higher risks of 1-year mortality (adjusted HR 3.64, 0.90-14.78; 2.50, 1.19-5.26; and 1.99, 1.17-3.39, respectively) and poor functional outcome (adjusted OR 3.62, 1.08-12.19; 1.51, 0.85-2.70; and 2.25, 1.42-3.57, respectively) in all 3 subgroups with eGFR < 60, 60-89, and 90 mL/min/1.73 m(2). Conclusions: An OGTT-derived estimate of insulin resistance with the composite ISI, but not HOMA-IR, was independently associated with increased risks of 1-year mortality and poor functional outcome in non-diabetic ischemic stroke patients with different eGFR strata.